Nutritional considerations in children undergoing bone marrow transplantation

Bone marrow transplantation is often associated with multiple organ failure which is usually reversible. Oral mucositis and dysphagia, vomiting, diarrhoea, protein losing enteropathy, transient exocrine pancreatic impairment, hypoalbuminaemia, biochemical trace element and mineral deficiencies are all common following transplantation and have profound nutritional consequences. Malnutrition affects negatively the clinical outcome. Nutritional support is provided to malnourished patients and those who suffer deterioration in nutritional status despite the provision of dietetic counselling. Only a few randomised studies comparing enteral with parenteral nutrition after transplant exist. Both enteral tube feeding (in the absence of mucositis) and parenteral nutrition are effective in maintaining nutritional status. However, enteral nutrition is associated with a better nutritional response and fewer complications than parenteral. With existing enteral and parenteral nutrition regimens close monitoring of trace element and mineral status is required.     

Oral health of children undergoing allogeneic bone marrow transplantation

BACKGROUND: Mixed bone marrow chimerism reliably produces donor-specific transplantation tolerance for a variety of solid organ and cellular grafts. We used a rat heterotopic tracheal transplant model for chronic rejection to investigate whether mixed chimerism could successfully prevent obstructive airway disease. METHODS: Mixed allogeneic chimeras were prepared by reconstituting lethally irradiated Wistar-Furth (WF) recipients with a mixture of 5 x 10(6) T-cell-depleted syngeneic (WF) and 100 x 10(6) T-cell-depleted allogeneic (ACI) bone marrow cells (ACI + WF --> WF). Mixed chimerism was present in all animals 28 days after bone marrow transplantation. Donor-specific, syngeneic, or major histocompatibility complex (MHC)-disparate allogeneic tracheas were implanted in recipient's omentum and removed for histologic analysis 30 to 150 days after transplantation. RESULTS: At 30 days after implantation, median luminal obstruction grades (0=none, 4=complete) of syngeneic and allogeneic tracheas were 0 and 4, respectively. Donor-specific (ACI) tracheas implanted in chimeric (ACI + WF --> WF) recipients were remarkably free of obstruction (median luminal obstruction grade=0 at 150 days) and had excellent preservation of respiratory epithelium. Third-party F344 tracheas implanted in chimeric recipients developed progressive luminal obstruction (grade 2 at 30 days, grade 3 at 90 days). CONCLUSIONS: Mixed allogeneic chimerism induces donor-specific tolerance and prevents development of the characteristic fibroproliferative obstructive lesion of bronchiolitis obliterans in a rat heterotopic tracheal transplant model. Excellent preservation of tracheal structure and morphology was achieved across major and minor histocompatibility barriers.     

Hypophosphataemia in patients undergoing bone marrow transplantation

We studied the prevalence of hypophosphataemia (< 0.80 mmol/l) in seventeen patients who had undergone bone marrow transplantation (BMT). Thirteen (77%) of the seventeen patients had hypophosphataemia at some stage during the conditioning phase or after their BMT. Seven (41%) of the seventeen patients had hypophosphataemia in the peri-BMT period that is during the conditioning phase or within one week thereafter. Two of the patients showed severe hypophosphataemia (< 0.30 mmol/l). We suggest that plasma phosphate should be monitored in patients with a bone marrow transplant.     

Microbiology of sinusitis in patients undergoing bone marrow transplantation

As a result of increasing use of bone marrow transplantation and new cytotoxic chemotherapy, more patients have become susceptible to sinus disease caused by unusual organisms. Sinusitis caused by fungi and gram-negative bacteria can be difficult to treat, may lead to severe complications, and should be managed promptly in the bone marrow transplant patient. Here we present the results of 41 cultures of the paranasal sinuses obtained from 18 bone marrow transplant patients in whom sinusitis developed. The most common agents were gram-negative bacteria (56.7%), followed by gram-positive bacteria (26.7%) and fungi (16.6%). In 13 samples the cultures were negative. Nasal cultures were performed ipsilateral to the sinus drained in 28 cases. Concordance was obtained in only 5 (17.8%) samples. The antibiogram of the isolated agents from the maxillary sinuses in this series revealed that the most efficient antibiotics were those that covered gram-negative bacteria. Treatment was usually prolonged in these patients, and different antibiotics were necessary to clear infections from the sinuses. In conclusion, treating sinusitis in bone marrow transplant patients may be challenging. Considerations about the microbiology and antibiogram susceptibilities of this specific population should be kept in mind when dealing with such cases.     

Vascular endothelial lesion in patients undergoing bone marrow transplantation

Changes in endothelial cell activity are likely to play a role in the thrombotic complications of bone marrow transplantation (BMT) such as the development of veno-occlusive disease. Accordingly, we measured established plasma endothelial cell markers von Willebrand factor (vWf), soluble thrombomodulin (sTM), soluble ICAM-1 (sICAM-1), and possible inducers of these molecules, TNF alpha and elastase, in the plasma of 25 patients, 1 week before as well as 1 and 3 weeks after BMT. Compared to healthy age and sex-matched controls, patients exhibited increased vWf and sTM. One week after transplantation, there were significant increases in vWf and sICAM-1, with a significant fall in elastases. Three weeks after the transplantation, sICAM-1 and, to a lesser extent, vWf increased still further, whereas elastases were unchanged. There were no significant changes in sTM and in TNF alpha through the serial study. Our data suggest that before conditioning, vascular endothelium is damaged by both injury and activation, as seen by the variations of vWf and sTM. After transplantation, the enhancement of this damage seems to be more specifically related to activation, since we observed a strong subsequent increase in vWf and markedly in sICAM-1.     

Cyclosporine-related encephalopathy following allogeneic bone marrow transplantation

Idiopathic granulomatous hepatitis is a rare disease of unknown cause that is characterized by recurrent fevers and granuloma in the liver. Attempts to define an exact etiology of the fever of granulomatous hepatitis frequently do not yield a precise diagnosis. Idiopathic granulomatous hepatitis was confirmed after a thorough work up and negative cultures and serologies were obtained, and in the absence of another condition that could lead to granulomas in the liver. We have experienced a 67-year-old female patient who presented with prolonged fever for 2 months and revealed granuloma in liver biopsy. She was treated with glucocorticosteroid and defervescence resulted.     

Acute renal failure following bone marrow transplantation

The medial preoptic nucleus (MPN) is an essential site for the regulation of male sexual behavior. Previous studies using c-fos as a marker for neural activation have shown that copulation increased c-fos expression in the MPN. Neural activation was also present in brain regions that are connected with the MPN and are involved in male sexual behavior, including the posteromedial bed nucleus of the stria terminalis (BNSTpm), posterodorsal preoptic nucleus (PD), posterodorsal medial amygdala (MEApd), and parvocellular subparafascicular thalamic nucleus (SPFp). The present study investigated whether the copulation-induced, activated neurons in these brain regions are involved in the bidirectional connections with the MPN. Therefore, mating-induced Fos expression was combined with application of anterograde (biotinylated dextran amine) or retrograde (cholera toxin B subunit) tracers in the MPN. The results demonstrated that neurons in the BNSTpm, PD, MEApd, and SPFp that project to the MPN were activated following copulation. However, in males that displayed sexual behavior but did not achieve ejaculation, few double-labeled neurons were evident, although both retrogradely labeled neurons and Fos-immunoreactive cells were present. In addition, retrograde neurons that expressed Fos were located in discrete subdivisions within the brain regions studied, where Fos is induced after ejaculation. Likewise, anterogradely labeled fibers originating from the MPN were not distributed homogeneously but were particularly dense in these discrete subdivisions. These results demonstrate that copulation-induced Fos-positive neurons in specific subdivisions of the BNSTpm, PD, MEApd, and SPFp have bidirectional connections with the MPN. Taken together with previous findings, this supports the existence of a discrete subcircuit within a larger neural network underlying male sexual behavior.     

Varicella vaccination in children after bone marrow transplantation

Herpes zoster (HZ) is one of the most common complications after bone marrow transplantation (BMT) in children. Apart from treatment with antiviral drugs, effective prevention by active immunization with varicella-zoster virus (VZV) appears to be possible. In this study 15 patients were vaccinated with a live attenuated VZV vaccine (Varilrix) 12-23 months after BMT. The vaccine was well tolerated without adverse reactions. Chickenpox or HZ were not observed for up to 2 years after immunization. Eight out of nine seronegative patients seroconverted and in six virus-specific IgG could still be demonstrated 2 years later. The incidence of VZV diseases in 133 non-immunized children after BMT was 26.3%. Infections usually occurred within 18 months after BMT.     

Late pulmonary impairment following allogeneic bone marrow transplantation

The pulmonary function of 88 consecutive leukemic patients who had undergone allogeneic bone marrow transplantation (BMT) was studied beforehand, at 3 months, at 6 months, and annually thereafter until 5 years after grafting. The parameters for function which are indicative for obstructive and restrictive lung disease deteriorated in all patient groups during the first 3 to 6 months after BMT but partially recovered within one year. Long-term decline in lung function was similar in all patient groups, and neither the onset nor the magnitude of pulmonary dysfunction was related to the occurrence of pulmonary impairment within 6 months after grafting. Multivariate analysis was then employed to assess predictors for long-term pulmonary disease. Despite the obvious effect of chronic graft versus host disease on the course of lung function, it was in itself not a significant predictor of long-term pulmonary outcome. Rather, the conditioning regimen turned out to be indicative; compared with busulfan, fractionated total body irradiation was demonstrated to be clearly superior with a lower incidence of both restrictive and obstructive long-term lung impairment. Our data indicate a previously unknown long-term side effect of busulfan conditioning.     

Cytomegalovirus prophylaxis and treatment following bone marrow transplantation

OBJECTIVE: To provide an overview of the role of cytomegalovirus (CMV) in the bone marrow transplant (BMT) population and update the current methods of prevention and treatment of CMV infection and disease, with emphasis on CMV interstitial pneumonia (CMV-IP). DATA SOURCES: The current medical literature, including abstracts presented at recent national and international meetings, is reviewed. References were identified by searching the MEDLINE database from January 1988 through June 1994. The reference lists of the published studies and reviews obtained from the initial literature search were reviewed as well. STUDY SELECTION: Data regarding the epidemiology of CMV, the risk factor associated with CMV infection and disease, as well as data on the prevention and the treatment of CMV infection and disease in the BMT population are cited. Specific attention was focused on randomized, placebo-controlled studies pertaining to the prevention of CMV infection and disease in CMV-immunoglobulin G positive recipients undergoing allogeneic BMT. Information from nonrandomized, placebo-controlled studies was included in the absence of stronger data. DATA EXTRACTION: Information contributing to CMV in the BMT population was reviewed. Data supporting and disputing specific preventive and treatment modalities are presented. DATA SYNTHESIS: The incidence of CMV seropositivity in the general population is high and while BMT becomes a widely accepted treatment modality, CMV reactivation and subsequent disease, especially CMV-IP, becomes a significant prognostic factor of morbidity and mortality. Even though antiviral agents such as ganciclovir and foscarnet can inhibit the viral replication in vivo, they have not been able to treat CMV-IP effectively. It has been suggested that CMV-IP is an immunopathologic process that can cause irreversible damage, hence, the low efficacy of antiviral therapy and the associated high mortality. Immunomodulating agents such as intravenous immune globulin and cytomegalovirus hyperimmune globulin can increase the efficacy of antivirals in the treatment of CMV-IP. This further supports the postulated immunopathologic process of this disease. The lack of understanding of the pathophysiology of the disease compromised the efforts of treatment and led to the development of preventive interventions with antiviral and immunomodulatory regimens that resulted in a significantly lower incidence of infection and disease. As a result of current data, the Eastern Cooperative Oncology Group has published guidelines for the prevention and treatment of CMV infection and disease. CONCLUSIONS: The prognosis of CMV disease in the BMT recipients has improved as a result of a wide variety of modifications in the management of BMT recipients. These include an increased understanding of the risk factors associated with CMV infection, routine screening for CMV replication and excretion, and more effective prophylactic regimens. Still, more than half of the patients who develop pneumonia will die, indicating that more studies are needed to increase the understanding of the pathophysiology and refine the preventive and therapeutic regimens against CMV.     

Fatal eosinophilic disease following autologous bone marrow transplantation

A 15-year-old girl developed massive, fatal eosinophilic disease following autologous bone marrow transplantation (BMT) for Hodgkin's disease (HD). Prior to autologous BMT, the erythrocyte sedimentation rate (ESR) was elevated, with active HD, but eosinophilia was absent. Post-autologous BMT, ESR and peripheral eosinophilia were observed to correlate with respiratory symptoms. Initial evaluation revealed no recurrent tumor, infection or other identifiable etiology. A diagnosis of chronic eosinophilic pneumonia was made following lung biopsy. A complete response was initially achieved with steroid therapy; however, when steroid therapy was tapered, the eosinophilia and elevated ESR recurred with worsening respiratory symptoms. Terminally, severe pulmonary disease developed and recurrent HD was found in lung, lymph nodes and bone marrow. During episodes of eosinophilia, the patient's serum stimulated her bone marrow as well as control marrow to produce predominantly eosinophilic colonies. Eosinophilic colony production was not observed with patient's sera obtained prior to or during autologous BMT or with control sera. This patient died of eosinophilic inflammatory disease following autologous BMT. The etiology of this disease was not definitely identified but appeared to be due to an eosinophilic-stimulating factor which developed after autologous BMT.     

Autologous bone marrow transplantation in children with advanced neuroblastoma

BACKGROUND: Encouraging results have been reported with high dose chemotherapy and total body radiation followed by bone marrow autotransplantation in children with advanced neuroblastoma; however, relapse remains a significant problem. METHODS: The authors treated 22 children with advanced neuroblastoma with high dose chemotherapy, surgery, intraoperative radiation, and a bone marrow autotransplant (treated in vitro to remove tumor cells) followed by 13-cis-retinoic acid. RESULTS: The 3-year relapse rate was 25% (95% confidence interval [CI], 6-44%). The 3-year disease free survival rate was 72% (95% CI, 52-92%). Toxicities included hemolytic uremic syndrome, herpes infection, and hepatic venoocclusive disease. CONCLUSION: These data suggest that this treatment strategy offers an increased rate of 3-year disease free survival. The nonrandomized nature of this study and its use of multiple modalities precludes the analysis of the specific contribution of each treatment component and comparison with conventional therapy.     

Skin manifestations of graft-versus-host reaction following bone marrow transplantation

We review the cutaneous manifestations of acute and chronic graft versus host disease (GvHD). Acute GvHD is characterized by initial itching, pain on pressure and erythema which begins on posterior auricular skin, palms and soles. The disease evolves into a typical but nonspecific maculopapular rash. Confluent rashes and follicular erythema may occur. Erosive oral lesions usually develop. The most severe variant of GvHD is toxic epidermal necrolysis, which often has a fatal outcome. The onset of chronic GvHD usually occurs more than 100 days after bone marrow transplantation and may be preceded by the acute form. The spectrum of skin changes includes lichenoid pruritic lesions with violaceous color and scleroderma-like skin involvement. Investigation of unknown rashes in these patients includes skin biopsy, which clearly differentiates leukocytoclastic vasculitis and erythema exsudativum multiforme with lymphocytic vasculitis from cutaneous manifestations of GvHD. Special stains may reveal bacteria and fungus in septicemic patients. The therapeutic options are discussed.     

Energy level and sleep quality following bone marrow transplantation

Hypothalamic-pituitary-adrenal (HPA) axis disturbances in depressed children with a history of abuse were examined. Thirteen depressed abused, 13 depressed nonabused, and 13 normal control children were given 1.0 microgram/kg of human corticotropin-releasing hormone (CRH) intravenously. Blood samples for corticotropin (ACTH) and cortisol were obtained at nine intervals. When compared to depressed nonabused and normal control children, depressed abused children had significantly greater peak, total, and net ACTH secretion post-CRH. Increased ACTH secretion was only observed in depressed abused children experiencing ongoing chronic adversity (marital violence, emotional abuse, poverty, lack of supports). The pattern of findings of the depressed abused children experiencing ongoing adversity parallels the pattern of HPA axis dysregulation reported in animal studies of chronic stress. They add to a growing body of literature suggesting measures of past trauma and current adversity are important sources of variability in psychobiological correlates of major depression.     

Reconstitution of cutaneous neural-immunological networks following bone marrow transplantation

Examination was made of the urinary and biliary excretion of the metabolites of genistein and genistein, the major components of Glycine and Sophora genus in rats. The urine of rats administered genistein orally contained eight metabolites. Three of these metabolites, genistein 4'-O-sulfate (M-1), genistein 7-O-beta-D-glucuronide (M-3), genistein 4'-O-sulfate 7-O-beta-D-glucuronide (M-6), were identified from spectroscopic and chemical data. The bile of rats administered genistein orally contained M-2, M-3 and M-6. M-6, a major biliary metabolite, was isolated and identified from spectroscopic and chemical data. The urine or bile of rats treated with genistein, the glycoside of genistein, contained M-1-M-8 or M-2, M-3, M-6 in the above metabolites. These findings suggest that genistein is absorbed as genistein after hydrolysis in the gastrointestinal tract. The total cumulative amounts of the two metabolites and genistein excreted in the urine during 48h, or of M-6 excreted in the bile during 36h following the oral administration of genistein, were approximately 5.7% or 16.0% of the doses administered, respectively. The result show that M-1, M-3 and M-6, having a free hydroxyl, glucuronide- or sulfate-conjugated hydroxyls at the C-7 or C-4' position, are excreted in the urine and bile as parts of the metabolites of genistein.     

Bronchoscopic evaluation of pulmonary infiltrates following bone marrow transplantation

Mutants of human prothymosin alpha with impaired ability to inhibit yeast Saccharomyces cerevisiae. cerevisiae cell growth were characterized. Two types of prothymosin alpha-inactivating mutations were observed. Mutations that belong to the first type compromised the nuclear entry of prothymosin alpha by affecting its nuclear localization signal. Analysis of subcellular distribution of GFP-prothymosin alpha fusions revealed a bipartite nuclear localization signal that is both necessary and sufficient for nuclear import of the protein in human cells. Mutations of the second type abrogated the inhibitory action of prothymosin alpha through an unknown mechanism, without influencing the nuclear import of the protein.     

Computer-controlled minute ventilation in preterm infants undergoing mechanical ventilation

INTRODUCTION: Computer-controlled minute ventilation (CCMV) continuously adjusts the ventilator rate to changes in spontaneous respiratory drive and pulmonary mechanics to maintain a preset total minute ventilation. HYPOTHESIS: We hypothesized that CCMV would maintain ventilation and oxygenation with fewer mechanical breaths than conventional intermittent mandatory ventilation in very low birth weight infants. METHODS: Very low birth weight infants in clinically stable condition who were undergoing mechanical ventilation were enrolled. The number of mechanical breaths, total and mechanical expiratory minute ventilation, mean airway pressure, oxygen hemoglobin saturation by pulse oximetry, and transcutaneous partial carbon dioxide and partial oxygen tensions were obtained during intermittent mandatory ventilation and CCMV (45 to 60 minutes) and compared by paired t test. RESULTS: Fifteen infants were studied. Birth weight (median, range) was 700 gm (550 to 1205 gm), gestational age 26 weeks (23 to 34 weeks), age 21 days (3 to 50 days). When switched from intermittent mandatory ventilation to CCMV, the number of mechanical breaths was reduced (15 +/- 2.8 to 8.6 +/- 2.9 breaths per minute, p < 0.001), leading to lower airway pressure (3.97 +/- 1.00 to 3.45 +/- 1.00 cm H2O, p < 0.001) and lower expiratory minute ventilation generated by the mechanical ventilator (116 +/- 31 to 65 +/- 28 ml/min per kilogram, p < 0.001), while total expiratory minute ventilation remained unchanged. Mean transcutaneous partial carbon dioxide and oxygen tensions, oxygen hemoglobin saturation, and the time spent within different oxygen hemoglobin saturation ranges did not differ between both ventilatory modes. CONCLUSION: CCMV maintained adequate ventilation and oxygenation with lower mechanical ventilatory support than IMV. CCMV may reduce barotrauma and chronic lung disease during long-term use.     

Bone mineral density in patients undergoing bone marrow transplantation for myeloid malignancies

Hitherto the biology of proteolysis in prokaryotes, particularly in archaea, is only poorly understood. We have used the tri-peptide vinyl sulfone inhibitor carboxybenzyl-leucyl-leucyl-leucine vinyl sulfone (Z-L3VS) to study the in vivo function of proteasomes in Thermoplasma acidophilum. Z-L3VS is a potent inhibitor of the Thermoplasma proteasome and is capable of modifying 75 to 80% of the proteasomal beta-subunits in cell cultures. Inhibition of proteasomes has only marginal effects under normal growth conditions. Under heat shock conditions, however, the effects of proteasome inhibition are much more severe, to the extent of complete cell growth arrest. These data suggest that other proteolytic systems may exist that can compensate for the loss of proteasome function in T. acidophilum.     

Long-term persistence of hemopoietic chimerism following sex-mismatched bone marrow transplantation

Wegener's granulomatosis is a distinct clinicopathologic entity characterized by granulomatous vasculitis of the upper and lower respiratory tract and glomerulonephritis. This disease can present as a clinical picture which resembles sepsis and adult respiratory distress syndrome (ARDS). Wegener's disease requires immunosuppression which can have detrimental consequences when used in sepsis. The following case report illustrates the diagnostic difficulties encountered by intensive care physicians treating severe pulmonary failure and multiple organ dysfunction in Wegener's granulomatosis appearing as ARDS with sepsis. CASE REPORT: A 19-year-old female patient had developed acute respiratory and renal failure after a prolonged period (many months) of antibiotic resistant otitis, sinusitis and mastoiditis. The patient had required intubation at another hospital and there was a history of tension pneumothorax and cardiopulmonary resuscitation during mechanical ventilation. Emergency extracorporeal membrane oxygenation (ECMO) for acute hypercapnic and hypoxic respiratory failure was instituted and the patient was transported to our institution while on ECMO. The patient was treated empirically for suspected pulmonary and systemic infection and received hydrocortisone (0.18 mg/kg/h) as part of a protocol-driven treatment of septic shock in addition to antibiotic and antimycotic regime. The use of ECMO was required for 10 and mechanical ventilation for another 50 days after admission. After successful extubation, central nervous system dysfunction became evident with a somnolent and generally unresponsive patient. When the hydrocortisone dose was gradually tapered, the clinical status of the patient further deteriorated, pulmonary gas exchange worsened and she developed renal failure with proteinura and hematuria. A renal biopsy was performed demonstrating vasculitis and focal segmental glomerulonephritis, a systemic granulomatous vasculitis was suspected; the serum was tested for anti-proteinase 3 antibodies (PR3-ANCA) and turned out to be positive (17.5 U/ml; normal range < 7 U/ml). The morphologic findings from renal biopsy, the positive test for antiproteinase 3 antibodies and the pulmonary-renal involvement with evidence of multisystem disease established the diagnosis of Wegener's granulomatosis. Immunosuppressive therapy with cyclophosphamide and prednisolone was instituted resulting in rapid improvement with recovery of pulmonary, renal and central nervous system function within two weeks. The use of ECMO in this patient served as a life-saving immediate measure usefull to "buy time" until a definite diagnosis could be established. ARDS represents an uniform pulmonary reaction to a large number of different noxious stimuli and disease entities. This case demonstrates that intensive care physicians caring for critically ill patients with ARDS should include even rare causes of pulmonary injury into their differential diagnosis.     

Unrelated donor bone marrow transplantation for children with acute leukemia

PURPOSE: To test the use of unrelated donor bone marrow transplantation (URD BMT) to cure children with high-risk acute leukemias. PATIENTS AND METHODS: Between June 1985 and December 1994, 50 children with acute leukemia (15 acute myelogenous leukemia [AML], 35 acute lymphoblastic leukemia [ALL]; 22 greater than second complete remission [CR]) received BMT from a URD at the University of Minnesota. Ages ranged from 0.9 to 17.5 years (median, 8.8). Median follow-up is 2.1 years (range, 1 to 7.3). Thirty patients (60%) received bone marrow fully matched at HLA-A,B and DRB1; 20 (40%) received bone marrow with a major or minor mismatch at a single HLA-A or B locus. RESULTS: The median time to neutrophil engraftment was day 24 (range, 14 to 42 days) in those receiving matched and day 25 (range, 15 to 32 days) in those receiving mismatched marrow (P = .35). The incidence of grades III to IV graft-versus-host disease (GVHD) was 23% (95% confidence interval [CI], 7% to 39%) in matched and 32% (95% CI, 8% to 52%) in HLA-mismatched patients (P = .57). The incidence of chronic GVHD was 50% (95% CI, 28% to 72%) in matched and 57% (95% CI, 23% to 91%) in mismatched patients (P = .80). Disease-free survival for patients with ALL is 37% (95% CI, 21% to 53%) at 1 year and 30% (95% CI, 15% to 46%) at 2 years; for patients with AML, 53% (95% CI, 28% to 78%) at 1 year and 33% (95% CI, 6% to 60%) at 2 years. CONCLUSION: URD BMT is an effective treatment for children with poor-prognosis acute leukemia and should be considered for all high-risk patients. Early referral of patients is strongly recommended.